Emerging applications of bioactive peptides and proteins in the treatment of periodontitis

Driven by oral pathogenic microorganisms, periodontitis is a chronic inflammatory disease, leading to progressive destruction of periodontal supporting tissues. Conventional therapies can alleviate symptoms, but are limited in their ability to eradicate pathogens, regenerate functional tissues, and prevent antibiotic resistance. Recent years have seen bioactive peptides and proteins (BAPPs) emerge as promising candidates for periodontitis treatment, owing to their multifunctional nature, excellent specificity, high biocompatibility, and favorable biodegradability. However, the enzymatic degradation of BAPPs leads to their short half-life in vivo. Therefore, rationally designed delivery strategies are indispensable to enhance the stability of BAPPs and improve targeting efficacy. This review summarizes the therapeutic mechanisms of BAPPs in periodontitis, including their antibacterial, immunomodulatory, antioxidant, and tissue-regenerating activities. It further explores advanced delivery strategies, such as nanoparticles, scaffold- or hydrogel-based platforms, and stimuli-responsive systems activated by pH, ROS, enzymes, light, or magnetic fields, to achieve the precise spatiotemporal control of BAPPs delivery. Additionally, the discussion further encompasses the clinical translational potential of BAPPs, alongside extant barriers and future outlook, thereby paving the way for more effective and safe periodontitis treatment strategies.